Mukopolisakkaridoz Hastalarının Geriye Yönelik Olarak Değerlendirilmesi: Tek Merkez Deneyimi

Bu çalışmada mukopolisakkaridoz tanısı ile izlediğimiz hastaların klinik, demografik ve laboratuvar verilerinin değerlendirilmesi amaçlanmıştır. Bursa Uludağ Üniversitesi Tıp Fakültesi Çocuk Metabolizma Hastalıkları Bilim Dalında mukopolisakkaridoz (MPS) tanısı ile izledi-ğimiz 41 hasta geriye yönelik olarak değerlendirilmiştir. Hastalarımızın dosyalarından MPS tipleri, tanı yaşları, güncel yaşları, cinsiyetleri, doğum ağırlığı, doğum şekli, büyüme ölçütleri, anne-baba arasındaki akrabalık düzeyi ve kardeş ölüm öyküsü kaydedilmiştir. Hastaların yaş ortalaması 9,41 ± 5,79 yıl (dağılım, 0,91-23 yıl) olarak saptanmıştır. Tanı alma yaşları 4,64 ± 4,01 yıl (dağılım, 0,50-19 yıl) olarak izlenmiştir. Hastaların 12’si (% 29,3) MPS tip 4a, 10’u (% 24,4) MPS tip 3, 7’si (% 17) MPS tip 6, 5’i (% 12,2) MPS tip 1, 5’i (% 12,2) MPS tip 2 ve 2’si (% 4,9) MPS tip 7 tanısı ile izlenmektedir. 22 (% 53,6) hastada akrabalık öyküsü, 4 hastada (% 9,7) de ise kardeş ölüm öyküsü mevcut idi. Hastaların 24’ünde (% 58,5) kardiyak tutulum, 19’unda (% 46,3) korneal bulanıklık saptanmıştır. Ayrıca 33 (% 80,5) hastada ‘dizostozis multipleks’ tespit edilmiştir. Sonuç olarak, çalışmamızda MPS tip 4a en sık izlenen tiptir. MPS tip 4a’nın en önemli fizik muayene bulgusu büyüme geriliği, kaba yüz görünümü ve iskelet deformiteleridir. Görüntülemede en önemli bulgu ‘dizostozis multiplekstir’. Hastalarımızdaki en sık kardiyak tutulum ise mitral yetmezlik olarak saptanmıştır.

Anahtar Kelimeler:

Mukopolisakkaridoz, Enzim Replasman Tedavisi, Mitral yetmezlik, Kaba yüz görünümü

Retrospective Evaluation of Patients with Mucopolysaccharidosis: A Single Center Experience

In this study, we aimed to evaluate the clinical, demographic and laboratory data of patients who were followed up with a diagnosis of mucopolysaccharidosis. 41 patients were evaluated retrospectively which followed up with the diagnosis of mucopolysaccharidosis in the Department of Pediatric Metabolism, Faculty of Medicine, Bursa Uludağ University. MPS types, age of diagnosis, current age, gender, birth weight, mode of delivery, growth metrics, parental consanguinity and sibling death history were recorded from the files of our patients. The mean age of the patients was found to be 9.41 ± 5.79 years (range, 0.91-23 years). The age at diagnosis was 4.64 ± 4.01 years (range, 0.50-19 years). Of the patients, 12 (29.3%) MPS type 4a, 10 (24.4%) MPS type 3, 7 (17%) MPS type 6, 5 (12.2%) MPS type 1, 5 (12.2%) were followed up with MPS type 2 and 2 (4.9%) with MPS type 7. There was a consanguinity history in 22 (53.6%) patients, and a history of sibling death in 4 (9.7%) patients. Cardiac involvement was found in 24 (58.5%) of the patients, and corneal blurring was found in 19 (46.3%). In addition, dysostosis multiplex was detected in 33 (80.5%) patients. In conclusion, MPS type 4a was the most common type in our study. The most important physical examination findings of MPS type 4a were growth retardation, coarse facial appearance and skeletal deformities. The most important finding in imaging was dysostosis multiplex. The most common cardiac involvement in our patients was determined as mitral insufficiency.

Keywords:

Mucopolysaccharidosis, Enzyme Replacement Therapy, Mitral insufficiency, Coarse facies,

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1. Khan SA, Peracha H, Ballhausen D, et al. Epidemiology of mucopolysaccharidoses. Mol Genet Metab 2017;121(3):227-240.
2. Scott HS, Bunge S, Gal A, et al. Molecular genetics of mucopolysaccharidosis type I: diagnostic, clinical, and biological implications. Hum Mutat 1995; 6:288.
3. Prasad VK, Kurtzberg J. Transplant outcomes in mucopolysaccharidoses. Semin Hematol 2010; 47:59.
4. Fraldi A, Serafini M, Sorrentino NC, et al. Gene therapy for mucopolysaccharidoses: in vivo and ex vivo approaches. Ital J Pediatr 2018; 44:130.
5. Elmonem MA, Mahmoud IG, Mehaney DA, et al. Lysosomal storage disorders in egyptian children. Indian J Pediatr 2016;83:805-13.
6. Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of lysosomal storage disorders. JAMA 1999;28:249-54.
7. Chiong MA, Canson DM, Abacan MA, et al. Clinical, biochemical and molecular characteristics of Filipino patients with mucopolysaccharidosis type II-Hunter syndrome. Orphanet J Rare Dis 2017;12:7.
8. Baehner F, Schmiedeskamp C, Krummenauer F, et al. Cumulative incidence rates of the mucopolysaccharidoses in Germany. J Inherit Metab Dis 2005;28:1011-7.
9. Kisa P, Kose E, Ateşoğlu M, Arslan N. Evaluation of Demographic and Clinical Characteristics of Patients with Mucopolysaccharidosis. The Journal of Pediatric Research 2017; 4: 59-62.
10. Kılıç M, Kalkanoğlu Sivri SH, Tokatlı A, Dursun A, Coşkun T. Mukopolisakkaridozlar: 3 Yıllık Hacettepe Deneyimi. J LSD 2010;2:83.
11. Koca S, Okur I, Eminoglu TF, ve ark. Gazi Üniversitesi Tıp Fakültesi Çocuk Beslenme ve Metabolizma Bilim Dalı’nda takip edilen mukopolisakkaridozlu hastaların klinik ve laboratuar özellikleri. J LSD 2008;1:81-3.
12. Wraith JE, Beck M, Lane R, et al. Enzyme replacement therapy in patients who have mucopolysaccharidosis I and are younger than 5 years: results of a multinational study of recombinant human alpha-L-iduronidase (laronidase). Pediatrics 2007;120:e37_46.
13. Clarke LA, Wraith JE, Beck M, et al. Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I. Pediatrics 2009;123:229_40.
14. Muenzer J, Wraith JE, Beck M, et al. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med 2006;8:465-73. Erratum in: Genet Med 2006;8(9):599.
15. Harmatz P, Giugliani R, Schwartz I, et al. Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study. J Pediatr 2006;148:533_9.
16. Burton BK, Whiteman DA. On behalf of the HOS Investigators. Incidence and timing of infusion-related reactions in patients with mucopolysaccharidosis type II (Hunter syndrome) on idursulfase therapy in the real-world setting: a perspective from the Hunter Outcome Survey (HOS). Mol Genet Metab 2011;103: 113-20.
17.Peters C, Shapiro EG, Anderson J, et al. Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. The Storage Disease Collaborative Study Group. Blood 1998; 91:2601-8.
18. Sawamoto K, Álvarez González JV, Piechnik M, et al. Mucopolysaccharidosis IVA: Diagnosis, Treatment, and Management. Int J Mol Sci 2020;21(4):1517.
19. Shapiro EG, Lockman LA, Balthazor M, Krivit W. Neuropsychological outcomes of several storage diseases with and without bone marrow transplantation. J Inherit Metab Dis 1995; 18:413-29.